Characterization of sgce6, the flavin reductase component supporting fad-dependent halogenation and hydroxylation in the biosynthesis of the enediyne antitumor antibiotic c-1027

Academic Article
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publication date

  • 2009

abstract

  • The C-1027 enediyne antitumor antibiotic from Streptomyces globisporus possesses an (S)-3-chloro-5-hydroxy-beta-tyrosine moiety, the chloro- and hydroxy-substituents of which are installed by a flavin-dependent halogenase SgcC3 and monooxygenase SgcC, respectively. Interestingly, a single flavin reductase, SgcE6, can provide reduced flavin to both enzymes. Bioinformatics analysis reveals that, similar to other flavin reductases involved in natural product biosynthesis, SgcE6 belongs to the HpaC-like subfamily of the Class I flavin reductases. The present study describes the steady-state kinetic characterization of SgcE6 as a strictly NADH- and FAD-specific enzyme.